Heretofore, many anticancer agents, including natural products, proteinergic or peptidergic agents, and synthetic small molecules, have been developed and used. However, most of these anticancer agents cause serious side effects on living normal cells and may not act on some types of carcinomas. In general cases, the actions of the anticancer agents vary in patients with the same type of carcinoma. Under such circumstances, numerous world-wide studies have been conducted on development of new concepts of anticancer agent that can provide a solution to the aforementioned problems, is able to selectively remove cancer cells without affecting living normal cells, and even can eliminate any type of cancerous cells.
Transcription factor CP2c, also termed CP2, Tfcp2, LSF, LBP1 or UBP1, is widely expressed in mammals. The activity of CP2c is elaborately regulated as cells progress from the resting phase (G0) into the DNA replication phase (S) and is essential in allowing cells to effectively progress through the G1/S transition phase. The regulation of CP2c activity is mostly achieved through post-translational modifications, and its levels are kept low in the norm. However, since CP2c is overexpressed in tumor cells, it serves as an important oncogene that plays a key role in carcinogenesis. In this connection, a research group at Boston University reported Factor Quinolinone Inhibitor 1 (FQI1) as a substance that inhibits the cellular activity of CP2c in liver cancer cell lines. FQI1 and its derivatives were identified by chemical library screening and were successful in selectively inhibiting cancer cells in cell and transplanted mouse models without affecting normal cells (Grant et al., Antiproliferative small-molecule inhibitors of transcription factor LSF reveal oncogene addiction to LSF in hepatocellular carcinoma, Proc. Natl. Acad. Sci. 2012; 109(12): 4503-4508).
Further, the present inventors have reported four novel peptide motifs (HXPR, PHL, ASR, and PXHXH) that were shown by screening of a peptide display library to recognize distinct regions of CP2c (Kang et al., Identification and characterization of four novel peptide motifs that recognize distinct regions of the transcription factor CP2, FEBS Journal 2005; 272:1265-1277). The present inventors have suggested that CP2c recognizes specific binding motifs of a target protein and interacts with the protein to regulate various cellular activities. In their follow-up study, the present inventors have screened peptides inhibiting the binding of CP2c to DNA through in vitro assay based on a DNA immunoprecipitation method that is useful for highly specific and sensitive analysis of DNA-protein interactions, and as a result, found that Peptide 5 composed of 12 amino acids inhibits CP2c-DNA binding in a concentration-dependent manner (Kim et al., A DNA immunoprecipitation assay used in quantitative detection of in vitro DNA-protein complex binding, Analytical Biochemistry. 2013; 441: 147-151).